German - Immune System Failure Flashcards
How do pathogens evade the immune system? 5
Serotype diversity
Antigenic drift
Antigenic shift
Gene conversion
Latency
Avoid the immune system
How do pathogens subvert the immune system? 6
Endocytic hijacking
Protein mimicry
Humoral inhibition
Inflammation inhibition
Immunosuppression
Superantigens
*COMMANDEER the immune system
What is serotype diversity?
Antigenically different strains of the same pathogen
- High genetic variability
- Not necessarily highly mutable
- Useful for tracking outbreaks
What is an example of serotype diversity?
One serotype of S. Pneumoniae infects
-Antibody response clears the infection
Another serotype infects
-Body has to now clear a second infection
What is antigenic drift?
Mutation in the viral genome driven by selective pressure as the virus infects a population
- Viral genomes are highly mutable
- Tied to memory erosion
- Responsible for viral epidemics
Example of antigenic drift?
Influenza spreading thru a GEOGRAPHICAL population
-Antibody binding to hemagglutinin prevents virus V form infecting a person
—It can mutate and now the body can’t prevent infection
What is antigenic shift?
Genetic recombination that leads to significant change in viral antigens
-Responsible for viral PANDEMICS
—Two separate viruses that fuse together
—Chicken infected with chicken flu and human flu will have the two viral genomes recombining which results in a new, potent virus
What is gene conversion?
Trypanosomes change cell surface glycoprotein expression
So, they just “shift” to the next VSG
VSG gene rearrangement
- One VSG is dominant at any time
- Minority express other VSGs
Humoral evasion
Population cycling with VSG expression
Epidemic is within _________
Pandemic is _________
A nation/area
Global
What is VSG?
Variable surface glycoprotein
What is latency?
Viral dormant state in host tissue
- Immune privileged tissue
- Reduced viral load
- Absent or reduced IFN response and MHC I expression
- NK and CD8 T cell evasion
Examples of latency?
HSV CMV VZV EBV Parvoviruses Adenoviruses
What cause recurrent emergence?
Stress
Concurrent infection
Compromised immunity
What is endocytic hijacking?
Utilize endocytosis for cellular entry
Prevent lysosome fusion
Escape phagosomes
Survive autolysosomal environment
What is antigen mimicry?
Adult worms coat themselves in host protein
Surface antigens are regularly shed
Antibody evasion and removal
What are superantigens?
Potent toxins that disrupt immune fx
G+ bacteria
- Staph A
- Strep pyogenes
Non-specific T cell activation
- Randomly activated
- Adaptive immune system “ramps” up for nothing
Ab and complement INACTIVATION
What is primary immunodeficiency?
Genetically caused immune system deficiency
What are the 3 types of primary immunodeficiency?
Dominant
Recessive
X-linked
What is secondary immunodeficiency?
Immune deficiency caused by environmental factors -Chronic disease -Immunosuppressive drugs -Viral —HIV -Environmental toxins
What are 4 viral strategies for subversion?
Inhibition of humoral immunity
- Virally encoded Fc receptor
- HSV, CMV, Vaccinia
Inhibition of inflammatory response
- Virally encoded chemokine receptor homolog
- CMV, Vaccinia, EBV
Blocking of antigen processing and presentation
- Inhibition of MHC I upregged by IFN-gamma
- HSV, CMV
Immunosuppression of host
- Virally encoded cytokine homolog of IL-10
- EBV
In primary immunodeficiency, there are dominant and recessive alleles.
Tell me about recessive immunodeficiencies.
Tell me about dominant immunodeficiencies.
Recessive - 2 recessive alleles for deficiency
Dominant - 1 dominant allele for deficiency
What kinase is associated with X-linked disorders?
Bruton’s tyrosine kinase (BTK)
Tell me what BTK is necessary for?
B cell signaling
BTK is on the ____ chromosome.
BTK males and homozygous females do not develop ____ ________.
BTK heterozygous females are ___________.
X
B cells
Carriers
What are the 5 classes of primary immunodeficiency?
Humoral immunity
Cellular immunity
Combined
Phagocytic cells
Complement
What does a kinase do?
Phosphorylates
Tell me about humoral immunity.
- 60%
- Reduced or absent serum immunoglobulin
- Impaired B cells
- Selective IgA deficiency is the most common
Tell me about cellular immunity.
-10%
-Impaired T cells
-Predisposition to viral, fungal, and opportunistic pathogens
-Most common
—DiGeorge Syndrome
—ZAP-70 deficiency
-X-linked lymphoproliferative syndrome
-Chronic mucocutaneous candidiasis
Tell me about combined primary immunodeficiency.
- 20%
- Deficiencies in both B and T cell fx
- Severe combined immunodeficiencies
Tell me about phagocytic cells in primary immunodeficiency.
-10%
-Impaired phagocytosis
-Frequent G- infections
-Most common
—Chronic granulomatous disease
—Leukocyte adhesion deficiency
—Chediak-Higashi syndrome
Tell me about complement in terms of primary immunodeficiency.
- Very rare (<2%)
- Deficiencies in complement components, inhibitors, or their production
- Recurrent bacterial infection
- Autoimmune disorders
HIV leads to ________.
AIDS
Tell me about HIV/AIDS.
Secondary immunodeficiency
Highly mutable
-Change rapidly and regularly
Blood and sexual fluid transmission
Targets CD4 T cells
-These are most common in the blood
-These are needed to mobilize adaptive immunity
—Antibody production is greatly affected
*Once the body does develop a response to the virus, the HIV then changes serotype and develops a “new” virus
—This leads to death
T/F -HIV is a retrovirus.
TRUE
